Related Experiment Video

Updated: Oct 19, 2026

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
00:06

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

Published on: September 12, 2019

Mutation of beta-catenin is an early event in chemically induced mouse hepatocellular carcinogenesis

T R Devereux1, C H Anna, J F Foley

  • 1Laboratory of Molecular Carcinogenesis, NIEHS, Research Triangle Park, North Carolina, NC 27709, USA.

Oncogene
|September 1, 1999
PubMed

Insights

Chemicals like methyleugenol, methylene chloride, and oxazepam activate beta-catenin, a key protein in Wnt-signaling, promoting liver cancer development in mice. These mutations appear to be early events in carcinogenesis.

Area of Science:

  • Hepatocellular Carcinogenesis
  • Molecular Biology
  • Toxicology

Background:

  • Beta-catenin activation and Wnt-signaling are crucial in various cancers.
  • Mutations in the beta-catenin gene, particularly at GSK-3beta phosphorylation sites, are implicated in hepatocellular neoplasms.
  • Understanding these mutations is key to identifying early events in liver cancer development.

Purpose of the Study:

  • To investigate mutations in the beta-catenin gene in hepatocellular neoplasms from B6C3F1 mice exposed to different chemicals.
  • To determine the chemical-specific involvement of beta-catenin activation in mouse liver carcinogenesis.
  • To assess whether beta-catenin alterations are early events in hepatocellular carcinogenesis.

Main Methods:

  • Analysis of 152 hepatocellular neoplasms from B6C3F1 mice across five chemical treatment groups and controls.
  • Sequencing of the beta-catenin gene to identify point mutations at specific codons (32, 33, 34, 41).
  • Western blot and immunohistochemistry to analyze beta-catenin protein expression and localization.

Main Results:

  • Significant point mutations in beta-catenin were found in neoplasms from mice treated with methyleugenol (20/29), methylene chloride (9/24), and oxazepam (18/42).
  • Fewer mutations were observed in liver tumors induced by vinyl carbamate (3/18), TCDD (1/18), and spontaneous neoplasms (2/22).
  • Beta-catenin protein accumulation along cell membranes was observed following mutations, indicated by Western blot and immunohistochemistry.

Conclusions:

  • Beta-catenin activation shows chemical-specific involvement in mouse hepatocellular carcinogenesis.
  • Mutations in beta-catenin occur in both adenomas and carcinomas, suggesting they are early events.
  • Altered beta-catenin expression and localization are associated with early stages of liver cancer development in mice.

More Related Videos

A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer06:01

A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer

Published on: July 6, 2017

Analysis of Liver Microenvironment During Early Progression of Non-Alcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma in Zebrafish09:27

Analysis of Liver Microenvironment During Early Progression of Non-Alcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma in Zebrafish

Published on: April 1, 2021

Related Concept Videos

Catenins01:23

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...
Mutagenicity and Carcinogenicity01:25

Mutagenicity and Carcinogenicity

Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
In-vitro Mutagenesis (Gene Knockouts)02:29

In-vitro Mutagenesis (Gene Knockouts)

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
Mouse Models of Cancer Study02:43

Mouse Models of Cancer Study

Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...